Alveolar soft part sarcoma (ASPS) is a rare soft-tissue malignancy constituting less than 1% of soft-tissue sarcomas with only about 25% of those occurring in the head and neck [
This IRB-approved retrospective case series describes two patients with ASPS of the head and neck treated at the University of North Carolina. Both patients present with very rare locations for head and neck ASPS (the larynx and parotid gland) with only a few known cases reported in the literature [
A 27-year-old male presented to our hospital with a 3-year history of hoarseness. He reported that the hoarseness had been worsening over the past few months and was newly associated with increased throat clearing and an occasional eating-associated cough. The past history was otherwise unremarkable.
Head and neck physical examination was unremarkable without evidence of masses, lesions, or cervical adenopathy. Endoscopy was then performed for further assessment. Flexible fiberoptic laryngoscopy revealed a left-sided submucosal mass of the false vocal cord obstructing the view of the underlying left true vocal cord. Normal mobility of the true vocal cords was noted and there was good glottis closure with pronation. The rest of the laryngeal exam was unremarkable.
Computed tomography (CT) revealed a 1.5 × 1.2 × 1.5 cm avidly enhancing mass in the anterior left vocal cord (Figure
Axial (a) and sagittal (b) CT of the avidly enhancing mass in the anterior left vocal cord.
Microscopic examination of the biopsy specimen revealed a multilobulated spindle cell lesion. Many of the lobules were composed of nests of large polygonal cells containing finely granular eosinophilic cytoplasm and separated by delicate vessels. Based on the structure, the differential diagnosis included ASPS, perivascular epithelioid cell tumor (PEComa), or possibly metastatic carcinoma.
Immunohistochemistry then revealed negative staining results for epithelial membrane antigen (EMA), cytokeratin AE1/AE3, Cam 5.2, S-100, HMB-45, Melan-A, and smooth muscle actin, with rare cells positive for desmin. TFE-3 then showed diffuse nuclear positivity. These results narrowed the differential to ASPS or PEComa. To confirm the diagnosis, FISH analysis was then performed to evaluate for TFE-3 gene rearrangement. A characteristic feature of ASPS is the unbalanced TFE-3 translocation; however, in this case, the translocation was determined to be balanced, even on repeated analysis. Given the observed morphology and gene rearrangement results in the limited biopsy sample, PEComa was the preliminary diagnosis.
The patient was consented for excision of the mass via an endoscopic left vertical hemilaryngectomy excising the left true and false vocal cord. Intraoperatively, all frozen section margins were reported to be clear of tumor; however, on final pathologic analysis, two of the frozen section margins contained residual tumor. Also, now evaluating a larger sample, pathology concluded that the characteristic microscopic appearance and the immunohistochemical results should override the molecular results and made the final diagnosis of ASPS.
Laser reexcision was then performed to manage the initial positive margins, resulting in negative margins, and it was determined that no residual tumor was present in the reexcised specimen. Considering the initial positive margins, the narrow surgical field, and the inability to obtain wide margins while sparing the larynx, the multidisciplinary tumor board decided to include adjuvant radiotherapy in the treatment plan to reduce the risk of local recurrence. The patient received radiotherapy (59.4 Gy) at an outside hospital closer to home due to additional family support. He responded well to the therapy, had no complications, and is disease-free 4 months after the completion of treatment.
A 37-year-old female presented to our institution with a 2-year history of left cheek swelling. The swelling was located in the region of the parotid gland and was not associated with pain. The past history was otherwise unremarkable.
Head and neck physical examination revealed a 2 × 2 cm firm, nontender mass in the left parotid area. The mass did not appear to be fixed to the underlying tissues. No adenopathy was appreciated and the remainder of the exam was unremarkable. Flexible fiberoptic nasal laryngoscopy was then performed for further evaluation, also determined to be unremarkable. CT scan was previously obtained at an outside institution and was not available to report.
Fine-needle aspiration was then performed to evaluate the mass. The initial assessment reported the presence of oncocytic cells consistent with an oncocytoma. The patient was then consented for excision of the mass via a left superficial parotidectomy, which was completed with close surgical margins.
Microscopic examination of the excised mass revealed a 2.1 cm discrete, possibly encapsulated, tumor consisting of nests and sheets of large, moderately pleomorphic, and polygonal cells bounded by broad fibrous septae with abundant small vessels. The cells showed minimal nuclear pleomorphism, prominent single central nucleoli, and abundant clear to eosinophilic granular cytoplasm. Rare mitotic figures were also noted. The differential diagnosis included oncocytoma, myoepithelioma, melanoma, adult rhabdomyoma, and ASPS.
Immunohistochemistry then revealed focal reactivity to desmin with no reactivity for actin, S100, HMB45, keratin, synaptophysin, or chromogranin. This immunophenotype supported the diagnoses of adult type rhabdomyoma and alveolar soft part sarcoma and excluded the others. Periodic acid Schiff (PAS) staining was then performed revealing focal reactivity with some cells showing an intracytoplasmic crystalline material. It was then determined that the PAS positive structure combined with the desmin reactivity was most consistent with ASPS.
Since ASPS has a high metastatic rate, especially to the lung, chest CT was performed for staging and ruled out pulmonary metastases. Considering the close surgical margins, she then underwent adjuvant radiotherapy to a total dose of 63.4 Gy. There were no major complications from treatment. Since completion of radiotherapy she has had regular follow-up and has remained disease-free 168 months after the completion of her treatment.
Alveolar soft part sarcomas are extremely rare soft-tissue sarcomas, typically occurring in the deep soft tissues of the lower extremities, and are especially rare in the head and neck [
Clinical characteristics of the alveolar soft part sarcoma series.
Case | Age | Gender | Location | Tumor size | Symptoms |
---|---|---|---|---|---|
1 | 27 | Male | Larynx | 1.5 cm | Hoarseness |
2 | 39 | Female | Parotid gland | 2.1 cm | Enlarging mass |
For the diagnosis of ASPS, imaging combined with analysis of the histologic, immunochemical, and molecular genetic features is beneficial. On imaging, the tumor demonstrates low attenuation on noncontrast CT and strong tumor enhancement with contrast administration. TI- and T2-weighted MRI images typically show higher signal intensity than muscle while demonstrating tubular areas of flow voids, representative of rapid blood flow within the tumor [
Due to the rarity of ASPS of the head and neck, the optimal treatment plan has not been clearly elucidated. Currently, the main treatment of primary ASPS, like most soft-tissue sarcomas, is surgical removal using a wide-local excision with the goal of obtaining negative margins [
The role of radiotherapy has been controversial. Early studies reported no significant benefit with the addition of radiotherapy [
Treatment and outcomes of the alveolar soft part sarcoma series.
Case | Primary treatment | Margin status | Recurrence location | Time to recurrence | Disease-free survival |
---|---|---|---|---|---|
1 | Surgery + adjuvant radiotherapy | Positive | N/A | N/A | 4 months (Alive) |
2 | Surgery + adjuvant radiotherapy | Negative | N/A | N/A | 168 months (Alive) |
Conventional cytotoxic chemotherapy has been widely reported to have little benefit in the treatment of ASPS [
Despite current treatments, the long-term prognosis for ASPS has remained poor due to the high rate of metastatic disease. Lieberman et al. cited 2-year, 5-year, 10-year, and 20-year survival rates of 77%, 60%, 38%, and only 15%, respectively [
In conclusion, our study reports two cases of head and neck ASPS in extremely rare locations, the larynx and parotid gland. When presenting in rare locations such as these, diagnosis can be difficult and analyses of the histopathologic, immunohistochemical, and molecular genetic features are beneficial for confirmation. Due to its rarity in the literature, the optimal treatment for ASPS has yet to be clearly elucidated. The most evidence seems to conclude that wide-local excision with adjuvant radiotherapy is the best current therapy, though long-term survival remains poor. Hopefully, continued research into new therapies such as antiangiogenic agents, as well as stringent follow-up for late-metastatic detection, will improve the poor outcomes of ASPS.
The authors declare that there is no conflict of interests regarding the publication of this paper.